Liver cancer is one of the most common malignancies worldwide and a major cause of cancer-related mortality. With limited treatment options, there is an urgent need to explore novel therapeutic approaches. Medicinal plants are of great importance and have demonstrated significant pharmacological potential. The objective of the present study was therefore to evaluate the anticancer effect of Passiflora incarnata L. and Arctium lappa L. leaf extracts, in comparison with non-thermal plasma and iron oxide nanoparticles. Cell viability was assessed using the MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and protein expression of P53 and Bcl2 was analyzed by proteomic techniques, with β-actin as the loading control. The MTT assay revealed that P. incarnata and A. lappa leaf extracts reduced the cell viability of HepG2 cancer cells from 100 % to 85 % and 80 %, respectively in a dose-dependent manner (200 µL). The treatments, including leaf extracts, gliding arc plasma and nanoparticles, significantly reduced cell viability. These results were supported by genes expression of tumor-associated genes, including P53 (tumor suppressor gene) and Bcl2 (antiapoptotic gene). Non-thermal plasma treatment increased the transcription and protein expression of P53, thereby enhancing apoptotic response in the HepG2 cell line at 40, 60 and 80 sec, with corresponding viability reductions 74.33 ± 1.07 %, 82.53 ± 1.15 % and 88.05 ± 0.36 %, respectively. Regarding the effect of methanolic extracts of P. incarnata and A. lappa leaves, this study demonstrated that P. incarnata, A. lappa and iron oxide nanoparticles significantly increased P53 gene transcription, reaching 99.89 ± 0.40 %, 98.07 ± 1.08 % and 99.76 ± 1.10 %, compared with the control group (66.22 ± 2.08 %).